by Megan Carlson, Guest Blogger for the Oncofertility Consortium

My name is Megan, and I will be your guest blogger for today.

I’m a journalism graduate student who had the great pleasure of shadowing Dr. Teresa Woodruff Tuesday as part of my health and science reporting practicum.

As soon as I arrived at 8 AM, Dr. Woodruff and I hit the ground running– greeting and checking in with the entire staff, from the program managers to the researchers already diligently at work in the lab.  This daily process is part of Dr. Woodruff’s efforts to maintain open communication with the entire lab.

We next traipsed over to a large conference room, where a group of 15 mostly-female scientists were already gathered with coffee and notepads ready for the weekly staff meeting, called the “R3 Data Club.”  Dr. Woodruff insists the entire team (who are located in several different locations) meet via web conference each week to discuss developments in the lab and present their research.  This is another explicit effort by Dr. Woodruff to ensure her team acts on the same page and immerses younger team members in the mission and work of the lab.

While some of the nitty-gritty details flew over my head (my knowledge of science could probably fill a thimble), I was impressed by the engagement of the staff as they listened to and questioned postdoctoral fellow, Pam Monahan, PhD’s, presentation on interactions among signaling pathways leading to potential disruptions in follicle development (itself, a possible contributing factor topolycystic ovary syndrome).

After the meeting, we rushed off to a government relations teleconference where a group, including Sharon Green, executive director of the Women’s Health Research Institute (WHRI) and Nadia Johnson, a program manager, planned the Chicago and Springfield Women’s Health Week celebrations.  Dr. Woodruff quickly switched her hat from hard-nosed scientist, asking pointed questions to her researchers about gene signaling pathways, to politically-savvy division chief, strategizing about how to best promote gender-specific scientific research to legislators, scientists and other interest groups.

I spent the remainder of the day shadowing Dr. Woodruff as she discussed efforts to increase enrollment in the Illinois Women’s Health Registry–an initiative that seeks to overcome the lack of sex-specific scientific research by connecting female research participants and researchers— and then following program managers and researchers who introduced me to the work of the Oncofertility Consortium.

The day was an educational whirlwind.  I absorbed a flood of scientific information about infertility, fertility preservation, and the reproductive system (augmented by time I spent Monday in the reproductive fertility clinic of Dr. Mary Ellen Pavone, who works closely with Dr. Woodruff).  I also witnessed the behind-the-scenes political work, research, and coordination that function to produce the newest innovations in fertility treatment and women’s health.  It was fascinating to see all the cogs in the machine interact together to create these beneficial and progressive outcomes.

By Danielle Alyce Fanslow, Francesca Duncan, and Kate Timmerman

There are several methods of fertility preservation open to female cancer patients who wish to start a family after treatment including cryopreservation of oocytes, embryos and ovarian tissue. Cryopreservation is a method of preserving biological material by storing it at extremely low temperatures. Choosing a  fertility preservation method is highly patient-specific and depends on factors such as patient age, the availability of a partner, and/or the sensitivity of the tumor to hormones.  A good option for pre-pubertal patients and patients who must undergo treatment as soon as possible after diagnosis may be cryopreservation of ovarian tissue.  However, current techniques for tissue cryopreservation may be improved as only 22 successful pregnancies have resulted from this method [1].

A group of Oncofertility researchers at the Oregon National Primate Research Center (Ting, Yeoman, Campos, Lawson, and Zelinksi) together with cryopreservation experts (Mullen and Fahy) have been developing new methods for cryopreserving ovarian tissue with the focus on preserving follicle health and quality.  Findings from their most recent work was published in the journal Human Reproduction in an article entitled “Morphological and functional preservation of pre-antral follicles after vitrification of macaque ovarian tissue in a closed system.”  This work provides insight that may lead to improved clinical protocols for ovarian tissue cryopreservation.

The goal of cryopreservation is to minimize injury to cells from the freezing process while limiting the toxicity of cryoprotective agents [2]. The current protocol for ovarian tissue cryopreservation involves slowly freezing the tissue with low concentrations of cryoprotective agents to avoid ice crystal formation inside the cell but to allow ice formation outside the cell [1]. However, ovarian tissue has an abundance of cell types and important extracellular material making it more complex to freeze compared to isolated cells. Vitrification is a method of cryopreservation that can avoid ice crystal formation inside and outside of the cell by quickly freezing the tissue with a high concentration of cryoprotective agent [3].   This method holds tremendous promise in the setting of fertility preservation and has already been applied successfully and routinely to egg and embryo freezing. However, researchers must optimize ovarian tissue vitrificaiton before it can be used in a clinical setting.

As the amount of human ovarian tissue available for research is limited, the Zelinski group used a non-human primate model to study several variables in the vitrification process including the type and concentration of cryoprotective agent used, the cooling rate, and the warming rate.  As a means to assess the quality of the tissue in each experimental condition, the researchers isolated ovarian follicles from the tissue and used them for encapsulated in vitro follicle growth (eIVFG) – a technique that this group had previously applied successfully to the non-human primate.  The researchers then monitored follicle health, diameter, and hormone production.   Using these techniques and assays,  the Zelinski group was able to determine a set of variables that resulted in the healthiest ovarian tissue. Through the findings by the Zelinski group, the field is one step closer to developing a standard protocol for ovarian tissue vitrification that can potentially result in a high rate of successful pregnancies.

References:

1. Ting AY, Yeoman RR, Campos JR, Lawson MS, Mullen SF, Fahy GM, Zelinski MB. Morphological and functional preservation of pre-antral follicles after vitrification of macaque ovarian tissue in a closed system. Hum Repro. 2013. Feb 20^th Ahead of Print.
2. Pegg DE. The history and principles of cryopreservation. Semin Reprod Med. 2002 Feb;20(1):5-13.
3. Pegg DE. The role of vitrification techniques of cryopreservation in reproductive medicine. Hum Fertil (Camb). 2005. Dec;8(4):231-9.

By Yogesh Makanji

In an Australian first, Monash IVF specialists reported achieving pregnancy in a 43-year-old woman after transplanting her cryopreserved ovarian tissue. Professor Gab Kovacs, Director of Monash IVF, Melbourne Australia, reported that his team had restored fertility in a woman by transplanting her cryopreserved ovarian tissue, following which she resumed natural ovulation and was six weeks pregnant. In 2005, this woman had ovarian tissue cryopreserved prior to commencing breast cancer treatment. If successful pregnancy ensues then in another Australian first, this would be the first Australian baby born from transplanted ovarian tissue and 20^th in the world. In light of their success, Professor Kovacs went on further to recommend ovarian tissue cryopreservation as a reliable, cheaper and easier method of preserving fertility of cancer patients; compared to cryopreserving eggs or embryos.

Adding to the commentary, Dr. Lyndon Hale, Medical director of Melbourne IVF Clinic, Australia reported that they had successfully transplanted ovarian tissue in patients and only one had become pregnant. However, she had subsequently miscarried. Dr. Hale also sees the benefits of this technique for preserving fertility of cancer patients.

Another trend emerging from this article is the use of cryopreserved ovarian tissue as a way of preserving a women’s fertility indefinitely.  In addition, it has been suggested that ovarian tissue transplant in peri-menopausal women may delay or offset symptoms associated with menopause; hot flashes, osteoporosis, weight gain, etc. Neither Professor Kovacs nor Dr. Hale is advocating the use of ovarian tissue transplant for this purpose. Hormone replacement therapies are available to alleviate some of these menopausal symptoms.

Ovarian tissue cryopreservation is providing many young cancer patients the opportunity to preserve their fertility. Chemo and radiotherapy may adversely affect a women’s future fertility. Thereby, cryopreservation of ovarian tissue prior to cancer treatment protects a women’s future fertility.

Source: The Age http://www.theage.com.au/national/health/science-beats-fertility-clock-20121128-2aev2.html

Oncofertility is an interdisciplinary field at the intersection of oncology and reproductive science. While those two fields make up the breadth of this discipline, it only touches the surface of what future clinicians need in their academic repertoire to successfully navigate this field.  In “Preparing an Interdisciplinary Workforce in Oncofertility: A Suggested Educational and Research Training Program,” in Oncofertility Medical Practice: Clinical Issues and Implementation, author Christos Coutifaris, MD, PhD, argues that the education and training of oncofertility professionals should involve, “oncology, pediatrics, reproductive science and medicine, biomechanics, material science, mathematics, social science, bioethics, religion, policy research, reproductive health law, and cognitive and learning science.”

Going forward, the National Institute of Health (NIH) has an ambitious agenda requiring multifaceted scientists and clinicians properly trained in both research and medicine. Ideally, physicians would be trained not only clinically, but they would also be prepared for investigative careers. According to Dr. Coutifaris, “the ultimate goal is to prepare reproductive endocrinologists, pediatric and adult oncologists, and surgeons, for investigative careers that focus on the reproductive, endocrine, and fertility needs of cancer patients and survivors.” By doing so, oncofertility specialists would be at the forefront of translational medicine, further benefiting the reproductive outcomes of cancer patients.

Dr. Coutifaris presents a well-laid training program for future oncofertility specialists. This includes establishing an executive steering committee responsible for the overall direction of the program, an advisory board to aid and shape the content of the program, an expert and diverse group of faculty members to mentor trainees, and research training, specifically focusing on the human oocyte. There should also be a comprehensive program evaluation in place to monitor the success of the program.

Having a dedicated oncofertility program in place to ensure that fertility options for young cancer patients is factored into their cancer care, is imperative.  Training and educating the next generation of oncofertility specialists will lay the foundation for improved cancer care and reproductive outcomes. Read, “Preparing an Interdisciplinary Workforce in Oncofertility: A Suggested Educational and Research Training Program,” to learn more about educating the next generation of oncofertility specialists. Participate in our new series of CME-accredited Virtual Grand Rounds to increase communication and education among healthcare providers.

Talking with teenagers about fertility can be awkward and uncomfortable. Talking with teenagers and their families about a cancer diagnosis is devastating. How do we do both at the same time and ensure that the importance of fertility preservation is understood in light of the traumatic timing? Studies among adult cancer survivors show that fertility is their most prevalent concern, thus we need to develop a method for relaying this information to young cancer patients and their families in a timely and sensitive manner. In the article, “The Birds and the Bees and the Bank: Talking with Families Amidst a Cancer Diagnosis,” by Gwendolyn P. Quinn, Caprice A. Knapp, and Devin Murphy, in Oncofertility Medical Practice: Clinical Issues and Implementation, the authors propose using a new method for initiating these discussions.

Patients and their families often look to health care providers to guide them in their decision-making process. Receiving a cancer diagnosis is very traumatic and can leave both the patient and their parents in a highly emotional state. They may not remember all that they were told in that initial discussion, but unfortunately decisions need to be made in that moment that will have an impact on their life many years later. Depending on the cancer diagnosis and the treatment protocol, loss of fertility may be a consequence., and needs to be addressed.

Studies show that communicating with patients using interactive tools, increases a patients understanding of the information being presented. Additionally, understanding is further increased, specifically when individual decision-making is involved, using a values clarification exercise or tool. According to the authors, “A values clarification tool (VCT) is often used in environments in which a common shared vision or purpose is required, the goal of which may be to develop the common vision, define roles, or develop long-range plans.” A VCT serves as a primer for future decision-making because it does not asks participants to ponder hypothetical situations, but instead aids them in defining the values and beliefs that influence their behavior. The authors maintain, “The open-ended statements of the VCT encourage patient/parent and administrator to begin a dialogue so that the patient/parent may process the idea of having children first, and then consider their feelings about possibly not being able to have children in their future.”

Allowing young patients to take an active role in making decisions about their fertility by evaluating their own beliefs and behaviors, and processing the idea of potential infertility, can actually serve to empower their decision-making process. Studies show that adolescent and teenage cancer survivors have clear expectations about parenthood and having biological children, yet are not always able to fully express these desires. The VCT can be a helpful tool in initiating these types of discussions. Read, “The Birds and the Bees and the Bank: Talking with Families Amidst a Cancer Diagnosis.” Learn more about your fertility options by visiting our Virtual Patient Navigator.

We are happy to be hosting Helen Picton, BSc, PhD, FSB for her Virtual Grand Rounds presentation tomorrow, October 25th, 2012, at 10 AM Central Time, entitled, “From Basic Science to Clinical Application- the Facts and Future of Ovarian Cryopreservation for Fertility Preservation.”  Dr. Picton’s work focuses on characterizing ovarian follicles during growth and maturation, and the developmental competence of in vitro oocytes, and will inform her discussion of the research behind ovarian tissue freezing and how to apply that technique in a clinical setting now, and as we move forward with advancements in the reproductive field.

Receive free CME’s tomorrow by participating in tomorrow’s Virtual Grand Rounds (VGR) with the Oncofertility Consortium. VGR’s are live videoconferences with experts in the fields of reproduction, cancer, and oncofertility. They provide researchers, clinicians, and others the opportunity to hear emerging research findings from anywhere across the globe and participate through a live videochat. This year, the Oncofertility Consortium is also able to offer free CME credits to health care providers through these live virtual events.

At 10 AM, Central Time, click here to watch Dr. Picton present her Virtual Grand Rounds.

After nearly ten years of research, a team of 20 doctors and specialists at the University of Gothenburg in Sweden, have performed the first mother-to-daughter uterine transplants in two Swedish women.

The two women, both in their 30s, received new wombs donated by their mothers on September 15^th and 16^th without complications.  One of the women was born without a uterus, while the other, a cervical cancer survivor, had to have her uterus removed many years prior.

The uterine transplant procedure was developed as a reproductive technology to allow women of childbearing age, who lack a uterus, to bear children.    Both women began hormonal treatments for in-vitro fertilization before the surgery.  Frozen embryos will be thawed and transferred to their new wombs once doctors have determined that they are healthy enough to support a pregnancy.

According to the Centers for Disease Control (CDC), more than 600,000 hysterectomies are performed annually in the US.  Although the vast majority of hysterectomies are performed electively as a treatment for symptoms associated with gynecologic disorders, removal of the uterus is frequently recommended when cancer of the cervix, uterus, vagina, fallopian tubes and/or ovaries is invasive.  Similarly, hysterectomy is recommended in cases of uterine fibroid tumors, endometriosis and uterine prolapse.

Uterine transplants are unique amongst organ transplants in that they are not required as a life-saving intervention.  Because the procedure is not regarded as life-saving, researchers had to perfect the procedure to make it as safe as possible using non-human primates.  The first successful transplant for the team was reported via a series of publications lead by Mats Brannstrom around 2003.  The team of more than 10 surgeons who performed last weeks uterine transplants, trained together for several years first with mice, reporting successful pregnancy and offspring.  The team has since been successful in other animal models including baboons.

Although it is too soon to know, the mark of success for these transplants, and one performed last year by Turkish doctors using a womb from a cadaver, is a successful pregnancy.  If successful, the option of uterine transplant may affect thousands of women of reproductive age that have had to have their uterus removed due to uterine or cervical cancer, endometriosis, and those born without a uterus due to genetic disorders such as Turner’s Syndrome.

In 2006, the American Society of Clinical Oncology (ASCO) published fertility preservation guidelines for clinicians to follow when treating young cancer patients in response to the increased likelihood of young men and women at risk of losing their fertility due to cancer and its treatment. Nonetheless, studies show that many young cancer patients still are not receiving important information related to their fertility, which would allow them to make informed decisions on their course of treatment.  In a new study in Current Oncology, entitled, “Fertility Risk Discussions in Young Patients Diagnosed with Colorectal Cancer,” authors, A. Kumar, A. Merali, G.R Pond and K. Zbuk performed a retrospective chart review for patients less than 40 years of age with newly diagnosed colorectal cancer between 2000 and 2009, to identify the frequency of fertility preservation discussions.

The investigators reviewed eligible health charts for any indication that a fertility discussion had taken place after initial diagnosis. If there was a documented discussion, investigators then reviewed the charts to see if any follow-up had been done via an oncologist or a reproductive specialist.  Demographic and treatment information was extracted from the charts.

The study identified 59 patients who met all the criteria for inclusion (18-40yrs old, year of diagnosis, stage of cancer, type of treatment, etc). Of those 59 patients, 35 were men and 24 were women. Their average age was 34, and 95% of the selection had received chemotherapy treatment for their cancer.

The study found that only 20 of the 59 patients received fertility counseling and 2 of those 20 did not receive a follow-up discussion with a reproductive specialist. The study also found that age was the most important factor as to whether or not an individual received a fertility discussion. Men and women under the age of 35 were more likely to receive a fertility discussion than those over 35.  Finally, the investigators observed no significant difference in the frequency of discussions after 2006, when the ASCO guidelines were published.

The results of this study demonstrate that the fertility risks associated with colorectal cancer treatment and fertility perseveration options available to newly diagnosed cancer patients, were discussed infrequently.  As we know, fertility preservation options are available; however, unless a patient or their clinical team are proactive about exploring those options, young cancer patients may not be getting the pertinent fertility information they need in a timely fashion. This study highlights the need for more health care professionals to discuss fertility risks with their patients prior to undergoing cancer treatment.

Read, “Fertility Risk Discussions in Young Patients Diagnosed with Colorectal Cancer.”

In many women with recurrent breast cancer, the estrogen receptor(ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of their tumors changes between treatment for the primary tumor and relapse, a large retrospective study has found. The findings, published June 18 in the Journal of Clinical Oncology, support previous studies that have also detected changes in these biomarkers during cancer progression.

These three biomarkers help doctors choose the best treatments for individual women. Therefore, tumors that recur in the breast or appear elsewhere in the body should be biopsied “as a routine procedure” because the results may influence treatment decisions, recommended the authors led by Dr. Linda Lindström of Cancer Center Karolinska in Sweden.

Dr. Lindström and her colleagues used information from pathology reports for 1,010 women treated at three hospitals in Stockholm, all of whom had biopsies taken from their primary and recurrent breast tumors….Read the rest of the blog on our sister website at the Institute for Women’s Health Research.

About 70,000 adolescents and young adults (ages 15-39) are diagnosed with cancer each year in the United States. During cancer treatment, adolescents and young adults (AYA) may focus all of their energy on getting through treatment. Some may not have spent much time talking or thinking about life after cancer treatment, and the impact their cancer treatment may have on their survivorship. Life after treatment often presents a new set of challenges and fertility may be one of the challenges that survivors face once treatment ends and family planning begins.

The importance of fertility options for AYA’s diagnosed with cancer has not been lost on the National Cancer Institute (NCI), which is one of 11 agencies that compose the Department of Health and Human Services (HHS). The NCI, established under the National Cancer Institute Act of 1937, is the Federal Government’s principal agency for cancer research and training. Recently, the NCI featured oncofertility in the NCI Cancer Bulletin, a distinguished news source for the latest in cancer research, in an article entitled, “So Others May Benefit: Young Cancer Patients and Survivors Take Part in Oncofertility Research.”

Understanding fertility outcomes for the AYA cancer population is imperative to improving the cancer treatment process and ensuring that fertility preservation discussions become standard procedure in comprehensive cancer care. Fertility preservation is of special concern for AYA cancer patients, a group that historically has been underrepresented in clinical research studies. “So Others May Benefit: Young Cancer Patients and Survivors Take Part in Oncofertility Research,” explores the unique approach that the Oncofertility Consortium used to get their attention and increase AYA participation in clinical studies: social media.

The success of this new outreach effort can be seen in the Consortium’s Fertility Information Research Study (FIRST). FIRST is a fertility information research study for young women who are facing or have faced cancer treatment. Researchers want to learn more about how cancers and treatments affect the reproductive health of young survivors, and whether or not cancer survivors wish to have children in the future or not.

When FIRST was initially launched, researchers had some difficulty recruiting study participants, due to the challenges AYA’s pose to researchers (in other words – they can be hard to track down). After some initial brainstorming, they decided to utilize their relationships with some of the leading AYA advocacy groups such as Stupid Cancer and Imerman Angels to reach the AYA population. After the first posting about the study on Twitter and Facebook, researchers received 15 calls from cancer patients willing to participate. Today, FIRST has 200 participants and counting, many of them learning about the study via social media.

To learn more about how the Oncofertility Consortium is changing the face of comprehensive cancer care through social media, read “So Others May Benefit: Young Cancer Patients and Survivors Take Part in Oncofertility Research.”